This project is designed to determine the neurochemical and neuroanatomical nature of the substrate mediating cocaine abuse liability. It is assumed that cocaine is abused because of its properties as a reward or reinforcer; thus the aim is to determine the neural substrate which is necessary for cocaine reinforcement. It is hypothesized that a catecholamine mechanism is involved, and that this same catecholamine mechanism mediates the reinforcing properties of intracranial electrical stimulation. Drug and lesion studies are planned to determine the mechanisms responding to both rewards, with a cocaine self-administration paradigm emphasized when neurochemically selective methods are most important, and using an intracranial self-stimulation paradigm when neuroanatomically selective methods are more important. These studies are intended to define the neural target of cocaine reinforcement so that electrophysiological recordings of activity in the reinforcement systems can be made. Once the sites for this recording are known, it is planned to determine to what degree a variety of reinforcers, including both natural rewards and also other drugs of abuse, act on the same target system. The work will be done with rats; standard cocaine self-administration and intracranial self-stimulation techniques will be given catecholamine system lesions; lesions and stimulation locus will be confirmed by fluorescence histochemistry; lesion extent will be determined by standard histological techniques, fluorescence histochemistry, and fluorometric assays for catecholamines in the terminal areas of the target areas.